In both human populations and animal models, many photoreceptor-specific genes have been identified that, when mutated, trigger retinal degeneration. A major goal of the current research is to determine the impact of the disease-causing genes on the cellular workings of photoreceptors. This will lead to a better understanding of the onset and progression of the disease and may influence the design of therapeutic strategies. In Drosophila, as in vertebrates, missense changes in the rhodopsin gene underlie dominant forms of retinal degeneration. The Drosophila mutations are known to affect rhodopsin transport, and it is likely that similar trafficking mechanisms are affected in vertebrate rhodopsin-based diseases. This application will use Drosophila to carry out a molecular study of genes involved in rhodopsin maturation. In the first aim, the investigators will characterize the role of Rab6 in rhodopsin maturation. The second aim will use strategies successfully used to identify rab6 mutations to isolate mutations affecting other proteins involved in specific membrane-trafficking events. They will then describe their effect on rhodopsin and other photoreceptor proteins. The experimental approaches of specific aims one and two benefit from the development of techniques to create and analyze photoreceptors lacking essential gene functions. The third aim will analyze other genes that appear to be specifically required for rhodopsin maturation. They will both continue their characterization of these mutant alleles of these genes and devise strategies to molecularly clone the identified genes. Overall, the effort will describe molecular components involved specifically in rhodopsin maturation as well as general protein trafficking within photoreceptor cells. The work will generate new information on the process of protein trafficking and will result in a better understanding of rhodopsin-based and other retinal diseases.